Structural mechanism of Smad4 recognition by the nuclear oncoprotein ski:: Insights on Ski-mediated repression of TGF-β signaling

被引:167
作者
Wu, JW
Krawitz, AR
Chai, JJ
Li, WY
Zhang, FJ
Luo, KX [1 ]
Shi, YG
机构
[1] Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA
[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
关键词
D O I
10.1016/S0092-8674(02)01006-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Ski family of nuclear oncoproteins represses TGF-beta signaling through interactions with the Smad proteins. The crystal structure of the Smad4 binding domain of human c-Ski in complex with the MH2 domain of Smad4 reveals specific recognition of the Smad4 L3 loop region by a highly conserved interaction loop (I loop) from Ski. The Ski binding surface on Smad4 significantly overlaps with that required for binding of the R-Smads. Indeed, Ski disrupts the formation of a functional complex between the Co- and R-Smads, explaining how it could lead to repression of TGF-beta, activin, and BMP responses. Intriguingly, the structure of the Ski fragment, stabilized by a bound zinc atom, resembles the SAND domain, in which the corresponding I loop is responsible for DNA binding.
引用
收藏
页码:357 / 367
页数:11
相关论文
共 47 条
  • [1] c-Ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interaction with Smads
    Akiyoshi, S
    Inoue, H
    Hanai, J
    Kusanagi, K
    Nemoto, N
    Miyazono, K
    Kawabata, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (49) : 35269 - 35277
  • [2] The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation
    Bottomley, MJ
    Collard, MW
    Huggenvik, JI
    Liu, ZH
    Gibson, TJ
    Sattler, M
    [J]. NATURE STRUCTURAL BIOLOGY, 2001, 8 (07) : 626 - 633
  • [3] BOYER PL, 1993, ONCOGENE, V8, P457
  • [4] Crystallography & NMR system:: A new software suite for macromolecular structure determination
    Brunger, AT
    Adams, PD
    Clore, GM
    DeLano, WL
    Gros, P
    Grosse-Kunstleve, RW
    Jiang, JS
    Kuszewski, J
    Nilges, M
    Pannu, NS
    Read, RJ
    Rice, LM
    Simonson, T
    Warren, GL
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1998, 54 : 905 - 921
  • [5] Structural and biochemical basis of apoptotic activation by Smac/DIABLO
    Chai, JJ
    Du, CY
    Wu, JW
    Kyin, S
    Wang, XD
    Shi, YG
    [J]. NATURE, 2000, 406 (6798) : 855 - 862
  • [6] Colmenares C, 1990, Semin Cancer Biol, V1, P383
  • [7] ACTIVATION OF THE C-SKI ONCOGENE BY OVEREXPRESSION
    COLMENARES, C
    SUTRAVE, P
    HUGHES, SH
    STAVNEZER, E
    [J]. JOURNAL OF VIROLOGY, 1991, 65 (09) : 4929 - 4935
  • [8] THE SKI ONCOGENE INDUCES MUSCLE DIFFERENTIATION IN QUAIL EMBRYO CELLS
    COLMENARES, C
    STAVNEZER, E
    [J]. CELL, 1989, 59 (02) : 293 - 303
  • [9] Transforming growth factor β-inducible independent binding of SMAD to the Smad7 promoter
    Denissova, NG
    Pouponnot, C
    Long, JY
    He, DM
    Liu, F
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) : 6397 - 6402
  • [10] The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for Smad3 in TGF-β-induced transcriptional activation
    Feng, XH
    Zhang, Y
    Wu, RY
    Derynck, R
    [J]. GENES & DEVELOPMENT, 1998, 12 (14) : 2153 - 2163